Oligomer formation by Na+-Cl--coupled neurotransmitter transporters.

Na+-Cl--dependent neurotransmitter transporters (or neurotransmitter:Na+ symporters, NSS) share many structural and functional features, e.g. a conserved topology of 12 transmembrane spanning alpha-helices, the capacity to operate in two directions and in an electrogenic manner. Biochemical and biophysical experiments indicate that these transporters interact in oligomeric quaternary structures. Fluorescence resonance energy transfer (FRET) microscopy has provided evidence for a constitutive physical interaction of NSS at the cell surface and throughout the biosynthetic pathway. Two interfaces for protein-protein interaction have been shown to be important in NSS; these comprise a glycophorin-like motif and a leucine heptad repeat. Upon mutational modification of the latter, surface targeting is considerably impaired without concomitant loss in uptake activity. This supports a role of oligomer formation in the passage of the quality control mechanisms of the endoplasmic reticulum and/or Golgi. In contrast, oligomerisation is dispensable for substrate binding and translocation.